Voltage clamp experiments were carried out to determine the function and structure of ionic channels in single giant nerve fibers. Information was obtained about the position and properties of membrane ionic channel sites that limit conductances and determine ionic selectivity by an analysis of the interaction between current-carrying and blocking ions. The ability of various kinetic models to describe the flow of ions through open potassium channels was tested. Kinetics of ionic blocking of channels were studied to gain information about energy barriers crossed by ions entering channels, and about the nature of ion binding sites within the channels. Analogies between the kinetics of ionic currents across the nerve membrane and those seen in excitable lipid bilayer membrane preparations treated with channel forming agents were investigated. Evidence was obtained to indicate that membrane sodium current is mediated by a specific ion-site interaction.